Fucoidan JHCF4s from Hizikia fusiformis against ethanol-induced damage in vitro and in vivo.

Fucoidan has strong antioxidant and free radical scavenging activities. We successfully isolated the active fucoidan, JHCF4, from edible Hizikia fusiformis. The effects of high-temperature water-extracted (T-JHCF4) and cellulase-assisted extraction (C-JHCF4) of JHCF4 were compared and to demonstrate those potential for treating alcoholic liver disease (ALD). C-JHCF4 contained higher amounts of fucose, arabinose, rhamnose, mannose, and sulfate groups, whereas T-JHCF4 had a higher galactose content. Importantly, C-JHCF4 downregulated the expression of Bax, Caspase 3, and cytochrome C in alcohol-treated LO2 cells and upregulated Bcl-2 expression, indicating its protective effect via an apoptosis-related pathway. In vivo, C-JHCF4 protected alcohol-induced zebrafish from reduced reactive oxygen species production and cell death, further regulating malondialdehyde and glutathione levels. Collectively, T-JHCF4 has advantages in extraction, such as short extraction time and low cost, making it suitable for large-scale industrial production. C-JHCF4 exhibited a stronger hepatoprotective effect than T-JHCF4, indicating its suitability for treating ALD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-01865-4.